Anti-Glycation And Metabolic Protective Effects of Petasites japonicus Maxim Leaf Extract in Methylglyoxal-Drinking Mouse Model Through Attenuation of Advanced Glycation End Products Accumulation

Abstract

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound that promotes formation of advanced glycation end products (AGEs) and protein cross-linking, thereby contributing to metabolic dysfunction and insulin resistance. In this study, we investigated the anti-glycation effects of Petasites japonicus Maxim leaf (PJL) extract using cell-free glycation assays and evaluated its ability to alleviate MGO-induced metabolic alterations in vitro and in vivo. In cell-free assays, PJL extract significantly inhibited AGEs formation in the BSA-fructose system and suppressed the formation of AGEs-collagen cross-link. Moreover, PJL extract effectively broke pre-formed AGEs-collagen cross-links, indicating broad anti-glycation activity across early and late glycation stages. In AML-12 hepatocytes, co-treatment with MGO markedly increased the expression of the receptor for AGEs (RAGE) and elevated intracellular MGO-adduct levels, confirming the establishment of a dicarbonyl stress model. Notably, PJL extract concentration-dependently attenuated MGO-induced reactive oxidative stress, RAGE upregulation and cytoprotective capacities. In vivo, mice administered 1% MGO for 16 weeks showed increased serum MGO-adduct levels, elevated insulin tolerance test (ITT) area under the curve (AUC), reduced rate constant of ITT (kITT), and increased body weight and adipose mass. Co-administration of PJL extract lowered serum MGO-adducts and ITT AUC and showed improving tendencies in kITT, body weight, and adiposity. Collectively, PJL extract exerts potent anti-glycation activity across cell-free, cellular, and in vivo systems and alleviates MGO-induced dicarbonyl stress and metabolic disturbances. These findings support PJL extract as a promising functional material for improving AGEs-related metabolic disorders.